Incidence and prevalence of advanced colorectal neoplasia in Lynch syndrome.

BACKGROUND AND AIMS: Lynch syndrome (LS) is the most common hereditary cause of colorectal cancer (CRC) and endometrial cancer (EC). Although colonoscopy reduces CRC in LS, the protection is variable. We assessed the prevalence and incidence of neoplasia in LS during surveillance colonoscopy in the United States and factors associated with advanced neoplasia. METHODS: Patients with LS undergoing ≥1 surveillance colonoscopy and with no personal history of invasive CRC or colorectal surgery were included. Prevalent and incident neoplasia was defined as occurring <6 months before and ≥6 months after germline diagnosis of LS, respectively. We assessed advanced adenoma (AA), CRC, and the impact of mismatch repair pathogenic variant (PV) and typical LS cancer history (personal history of EC and/or family history of EC/CRC) on outcome. RESULTS: A total of 132 patients (inclusive of 112 undergoing prevalent and incident surveillance) were included. The median examination interval and duration of prevalent and incident surveillance was .88 and 1.06 years and 3.1 and 4.6 years, respectively. Prevalent and incident AA were detected in 10.7% and 6.1% and invasive CRC in 0% and 2.3% of patients. All incident CRC occurred in MSH2 and MLH1 PV carriers and only 1 (.7%) while under surveillance in our center. AAs were detected in both LS cancer history cohorts and represented in all PVs. CONCLUSIONS: In a U.S. cohort of LS, advanced neoplasia rarely occurred over annual surveillance. CRC was diagnosed only in MSH2/MLH1 PV carriers. AAs occurred regardless of PV or LS cancer history. Prospective studies are warranted to confirm our findings.

Clinically actionable findings on surveillance EGD in asymptomatic patients with Lynch syndrome.

BACKGROUND AND AIMS: Lynch syndrome (LS) predisposes patients to multiple cancers including of the gastric and small bowel. Data supporting EGD surveillance in LS are limited. Our aim is to describe upper GI (UGI) findings in asymptomatic LS patients undergoing EGD surveillance within a hereditary colorectal cancer registry. METHODS: Asymptomatic patients with LS who underwent ≥1 surveillance EGD were included. Demographics, genotype, and EGD findings were reviewed. The frequency of clinically actionable findings including neoplasia (cancer, adenomas), Barrett's esophagus (BE), Helicobacter pylori, and hyperplastic polyps >5 mm were assessed. RESULTS: Three hundred twenty-three patients underwent 717 EGDs starting at a median age of 49.5 years. On average, each patient had 2 EGDs with an interval of 2.3 years between examinations. Clinically actionable findings were identified in 57 patients (17.6%). On baseline EGD 27.7% of findings were identified, with the remainder on surveillance EGD over an average of 3.5 years. Five asymptomatic patients (1.5%) had an UGI cancer detected during surveillance, all at early stage, including 1 patient each with BE-related esophageal adenocarcinoma, gastric neuroendocrine tumor, and gastric adenocarcinoma and 2 patients with duodenal adenocarcinoma. Two cancers were found on baseline EGD and 3 on follow-up EGD. CONCLUSIONS: Clinically actionable findings were found in approximately 1 in 6 asymptomatic patients with LS undergoing EGD surveillance. Five patients (1.5%) were diagnosed with cancer, all detected at an early stage. These data suggest that both baseline and follow-up EGD surveillance are effective in detecting early-stage UGI cancers in asymptomatic patients with LS.

The burden of cost in inflammatory bowel disease: a medical economic perspective.

PURPOSE OF REVIEW: The cost of care for inflammatory bowel disease (IBD) has nearly doubled over the last two decades. With evolving treatment paradigms utilizing costly but efficacious biologic agents earlier and more often, the cost burden is only expected to worsen. The purpose of this review is to explore the current economic landscape and drivers of IBD healthcare costs along with potential mechanisms for improving value and cost-effectiveness of IBD care. RECENT FINDINGS: The prevalence of IBD continues to rapidly expand with costs following suit. As compensation models change, the medical community is more incentivized than ever to develop cost reduction strategies including incorporation of high-value care measures, cooperative data aggregation, and technological solutions, with many of these interventions demonstrating promising results. SUMMARY: IBD is an expensive chronic disease with payments only expected to rise. In light of this financial conundrum, new practice models, such as the IBD specialty medical home and remote telemedicine, are being tested with an emphasis on cost reduction. Many of these strategies are demonstrating improved patient outcomes while also curbing expenses. These early successes set the stage for continued cooperation, collaboration, and growth in value-based management of IBD.

The Burden of Cost in Inflammatory Bowel Disease: A Medical Economic Perspective and the Future of Value-Based Care.

PURPOSE OF REVIEW: To examine the quantifiable economic impact of inflammatory bowel disease (IBD), key cost drivers and determinants, and the impact of value-based care in IBD. Finally, we prognosticate on future directions and opportunities on healthcare economics in IBD. RECENT FINDINGS: New value-based initiatives, technologically driven interventions, and quality improvement programs have demonstrated reductions in healthcare utilization and enhanced patient outcomes, and several have realized cost of care reductions. IBD is a costly, chronic illness with unbalanced spending by a small proportion of individuals. Pharmaceutical costs are overtaking inpatient expenses as the primary cost driver. Value-based care initiatives including the IBD medical home, remote monitoring platforms such as myIBDcoach and Project Sonar, and learning healthcare networks exemplified by ImproveCareNow have all demonstrated successes in improving care quality, patient outcomes, and reduced healthcare spending in some populations. The future of value-based care in IBD is bright, with ample opportunities for model refinement, collaboration, and growth.

Systematic Review and Meta-analysis of Clinical Trials Examining the Benefit of Exercise Programmes Using Nordic Walking in Patients With Peripheral Artery Disease.

OBJECTIVES: An exercise programme is part of the initial management of peripheral artery disease (PAD). Nordic walking uses poles and a core-focused walking technique to reduce the load on the legs, which may have advantages as an exercise programme for PAD. This systematic review examined the benefit of a Nordic walking programme for treating PAD compared with other programmes. METHODS: A systematic approach was used to identify clinical trials comparing Nordic walking and control programmes in PAD patients. For inclusion, studies had to report maximum walking distance (MWD) measured with a treadmill test or corridor walking test both at entry and follow up. Study quality was appraised using the Cochrane collaboration tool for assessing risk of bias. An inverse variance weighted meta-analysis was performed to compare improvements in MWD. RESULTS: Five independent trials involving 294 patients were identified. In three trials, supervised Nordic walking programmes were compared with supervised standard walking. One trial compared a home based Nordic walking programme with a similar standard walking programme. One trial compared a partly supervised Nordic walking programme with best medical management. Meta-analysis of all data suggested that MWD improvements were similar for patients treated by Nordic and standard walking programmes (standardised mean difference, SMD = 1.31, 95% CI -1.28 to 3.91; p = .322). Findings for completely supervised programmes were similar to the primary analysis (SMD = -0.79, 95% CI -2.81 to 1.24; p = .446) while those from partially supervised or home based programmes favoured Nordic walking (SMD = 4.46, 95% CI 3.39, 5.53; p < .001), mainly due to results from one home based trial. CONCLUSIONS: This systematic review suggests no benefit of Nordic over standard walking as supervised exercise for PAD. Favourable results were reported for one home based Nordic walking programme. A larger trial is needed to assess whether this finding can be replicated or not.

Long-term outcomes after stenting versus endarterectomy for treatment of symptomatic carotid stenosis: the International Carotid Stenting Study (ICSS) randomised trial.

BACKGROUND: Stenting is an alternative to endarterectomy for treatment of carotid artery stenosis, but long-term efficacy is uncertain. We report long-term data from the randomised International Carotid Stenting Study comparison of these treatments. METHODS: Patients with symptomatic carotid stenosis were randomly assigned 1:1 to open treatment with stenting or endarterectomy at 50 centres worldwide. Randomisation was computer generated centrally and allocated by telephone call or fax. Major outcomes were assessed by an independent endpoint committee unaware of treatment assignment. The primary endpoint was fatal or disabling stroke in any territory after randomisation to the end of follow-up. Analysis was by intention to treat ([ITT] all patients) and per protocol from 31 days after treatment (all patients in whom assigned treatment was completed). Functional ability was rated with the modified Rankin scale. This study is registered, number ISRCTN25337470. FINDINGS: 1713 patients were assigned to stenting (n=855) or endarterectomy (n=858) and followed up for a median of 4·2 years (IQR 3·0-5·2, maximum 10·0). Three patients withdrew immediately and, therefore, the ITT population comprised 1710 patients. The number of fatal or disabling strokes (52 vs 49) and cumulative 5-year risk did not differ significantly between the stenting and endarterectomy groups (6·4% vs 6·5%; hazard ratio [HR] 1·06, 95% CI 0·72-1·57, p=0·77). Any stroke was more frequent in the stenting group than in the endarterectomy group (119 vs 72 events; ITT population, 5-year cumulative risk 15·2% vs 9·4%, HR 1·71, 95% CI 1·28-2·30, p<0·001; per-protocol population, 5-year cumulative risk 8·9% vs 5·8%, 1·53, 1·02-2·31, p=0·04), but were mainly non-disabling strokes. The distribution of modified Rankin scale scores at 1 year, 5 years, or final follow-up did not differ significantly between treatment groups. INTERPRETATION: Long-term functional outcome and risk of fatal or disabling stroke are similar for stenting and endarterectomy for symptomatic carotid stenosis. FUNDING: Medical Research Council, Stroke Association, Sanofi-Synthélabo, European Union.

Development of a modelled anatomical replica for training young neurosurgeons.

INTRODUCTION: The Modelled Anatomical Replica for Training Young Neurosurgeons (MARTYN) is a novel simulation model developed by the Royal College of Surgeons England (RCSEng). This study describes the development of the model and aims to determine its feasibility as a potential future training tool. METHODS AND MATERIALS: Traditional model-making methods were used to develop a prototype. Initial procedural trials tested the feasibility of the model. Eighteen participants, grouped by experience (nine novices, four intermediates and five experienced), completed two tasks: a craniotomy and a burr hole followed by insertion of an external ventricular drain (EVD). Subjective data on confidence, usefulness, realism and preference to other training modalities were collected via a standardised questionnaire and a 5-point Likert scale. RESULTS: Preliminary trials of the model prototype demonstrated feasibility. The novice group had the greatest self-reported benefit from MARTYN training, with significant increases in self-rated confidence in both the craniotomy (p < 0.01) and EVD insertion (p < 0.05) procedures. MARTYN was reported to having good visual and tactile realism overall with the bone component being considered highly realistic. The model was reported to be a useful training tool. When asked to rank preferred training modalities, operative experience was chosen first with cadaveric training and MARTYN consistently scoring a second choice. CONCLUSIONS: MARTYN was developed with the intention to fill the current niche for an inexpensive synthetic model head. This study shows that the use of MARTYN for training is both feasible and realistic. We demonstrate a preliminary face and construct validity of the model in this pilot study. With the reduction in working hours, we believe this model will be a suitable supplement to the current ST 1-3 level cadaveric training and will have a positive impact on patient safety.

Metastatic Neuroendocrine Neoplasms to the Pancreas: Two Unusual Cases and a Review of the Literature.

Neuroendocrine tumor metastases to the pancreas are rare, and they share substantial overlap with the significantly more common primary pancreatic neuroendocrine neoplasms, representing a potential diagnostic pitfall. Elucidating whether a neuroendocrine tumor within the pancreas is a primary neoplasm versus a metastasis has significant prognostic and treatment implications. Correlation with clinical history and imaging as well as incorporating an appropriate immunohistochemical panel are essential to establish the correct diagnosis. Herein, we present 2 rare neuroendocrine tumors that metastasized to the pancreas: a medullary thyroid carcinoma and an atypical carcinoid tumor of lung origin. We also provide a brief review of the literature.

In vitro toxicity and chemical analysis of e-cigarette aerosol produced amid dry hitting.

Dry hitting, a phenomenon produced by e-cigarettes with refillable cartridges when the liquid in the coil is low, is a common occurrence among regular vapers despite being an unintended consequence of the device. This phenomenon's hazard to public health is still unknown and needs further investigation. Lung cells cultured at the air-liquid interface were exposed to vaped aerosol consisting of 3 % w/v ethyl maltol in propylene glycol for three-second puffs every 30 seconds for 80 total puffs with either dry hit or saturated conditions. Cytotoxicity was measured colorimetrically. The thermal degradation of the heating coils and wicks was visualized using scanning electron microscopy. The chemical byproducts in the aerosol were analyzed using proton nuclear magnetic resonance and inductively coupled plasma mass spectrometry. The results revealed a highly significant increase in cytotoxicity from dry hit treatments. Imaging showed thermal decomposition of the cotton wick after dry hitting, which was confirmed by energy dispersive x-ray spectroscopy with less oxygen in the dry hit cotton. Chemical byproducts were found via unique peaks in the dry hit condensate in the aromatic and alkene regions. Saturated condensate showed higher concentrations of detected metal species than dry-hit condensate. E-cigarette users should avoid dry hitting by refilling tanks or cartridges preemptively or by using disposable coils to avoid increased toxicity during vaping.

Outcomes of Liver Transplantation in Patients With Preexisting Coronary Artery Disease.

BACKGROUND: Advances in surgical and medical technology over the years has made liver transplantation possible for older and higher risk patients. Despite rigorous preoperative cardiac testing, cardiovascular events remain a major cause of death after orthotopic liver transplantation (OLT). However, there are little data on the outcomes of OLT in patients with preexisting coronary artery disease (CAD). This study aimed to compare all-cause and cardiovascular mortality of patients with and without history of CAD undergoing OLT. METHODS: Six hundred ninety-three adult patients with cirrhosis underwent liver transplantation between July 2013 and December 2018 (female n = 243, male n = 450; median age 59). RESULTS: During the study period of 5 y (median follow-up, 24.1 mo), 92 of 693 patients (13.3%) died. All-cause mortality in the CAD group was significantly higher than in the non-CAD group (26.7% versus 9.6%; P <0.01). Cardiovascular events accounted for 52.5% of deaths (n = 21) in patients with CAD compared with 36.5% (n = 19) in non-CAD patients. At 6 mo, patients with combined nonalcoholic steatohepatitis (NASH)/CAD had significantly worse survival than those with CAD or NASH alone ( P <0.01). After 6 mo, patients with CAD alone had similar survival to those with combined NASH/CAD. CONCLUSIONS: Patients with preexisting CAD before liver transplantation are at higher risk of death from any cause, specifically cardiovascular-related death. This risk increases with coexisting NASH. The presence of NASH and CAD at the time of liver transplant should prompt the initiation of aggressive risk factor modification for patients with CAD.

Workplace-based assessment: the need for continued evaluation and refinement.

Workplace-Based Assessment (WBA) has been an integral part of the UK Intercollegiate Surgical Curriculum Programme (ISCP) since 2007 (www.iscp.ac.uk). The UK Postgraduate Medical Education and Training Board (now part of the General Medical Council) has defined WBA as 'the assessment of working practices based on what trainees actually do in the workplace, and predominantly carried out in the workplace itself' (www.gmc.org.uk). This article reviews the purpose of WBA and the methods in current use. It also discusses the misuse of WBA and possible solutions, including redesign of the rating scales.

Substituted cysteine scanning in D1-S6 of the sodium channel hNav1.4 alters kinetics and structural interactions of slow inactivation.

Slow inactivation in voltage-gated Na+ channels (Navs) plays an important physiological role in excitable tissues (muscle, heart, nerves) and mutations that disrupt Nav slow inactivation can result in pathophysiologies (myotonia, arrhythmias, epilepsy). While the molecular mechanisms responsible for slow inactivation remain elusive, previous studies have suggested a role for the pore-lining D1-S6 helix. The goals of this research were to determine if (1) cysteine substitutions in D1-S6 affect gating kinetics and (2) methanethiosulfonate ethylammonium (MTSEA) accessibility changes in different kinetic states. Site-directed mutagenesis in the human skeletal muscle isoform hNav1.4 was used to substitute cysteine for eleven amino acids in D1-S6 from L433 to L443. Mutants were expressed in HEK cells and recorded from with whole-cell patch clamp. All mutations affected one or more baseline kinetics of the sodium channel, including activation, fast inactivation, and slow inactivation. Substitution of cysteine (for nonpolar residues) adjacent to polar residues destabilized slow inactivation in G434C, F436C, I439C, and L441C. Cysteine substitution without adjacent polar residues enhanced slow inactivation in L438C and N440C, and disrupted possible H-bonds involving Y437:D4 S4-S5 and N440:D4-S6. MTSEA exposure in closed, fast-inactivated, or slow-inactivated states in most mutants had little-to-no effect. In I439C, MTSEA application in closed, fast-inactivated, and slow-inactivated states produced irreversible reduction in current, suggesting I439C accessibility to MTSEA in all three kinetic states. D1-S6 is important for Nav gating kinetics, stability of slow-inactivated state, structural contacts, and state-dependent positioning. However, prominent reconfiguration of D1-S6 may not occur in slow inactivation.

Which is the best revascularization for critical limb ischemia: Endovascular or open surgery?

This review considers the roles of endovascular and open surgery for critical lower limb ischemia. The TransAtlantic Inter-Society Consensus document offers sensible guidelines for the treatment of both suprainguinal and infrainguinal disease. For bilateral/diffuse suprainguinal disease, aortobifemoral bypass remains the best option, but great care should be taken in this new era of hospital-acquired infection. Unilateral iliac occlusions should be treated by primary stenting, but an iliofemoral or femorofemoral bypass may be the best option when the disease extends down into the common femoral artery. Stents may reduce the risk of embolization in iliac stenoses but probably confer no benefit in long-term patency. Iliac stenoses should be treated by angioplasty, with stents reserved for flow-limiting complications. Although infrainguinal bypass surgery is in decline, probably due to better medical treatment and more endovascular intervention, bypass using autologous saphenous vein remains the gold standard. In the absence of leg veins, arm vein should be considered. Prosthetic grafts should be used as a last resort, and only with a venous cuff. The long-term results of the Bypass Versus Angioplasty in Severe Ischemia of the Leg (BASIL) trial favor surgery rather than angioplasty if there is a good vein and the patient is fit. Further randomized studies of infrainguinal stenting vs bypass are required. Some patients with critical lower limb ischemia are best treated by analgesia or primary amputation.

A Randomized Controlled Trial to Compare e-Feedback Versus "Standard" Face-to-Face Verbal Feedback to Improve the Acquisition of Procedural Skill.

BACKGROUND: Constructive feedback plays an important role in learning during surgical training. Standard feedback is usually given verbally following direct observation of the procedure by a trained assessor. However, such feedback requires the physical presence of expert faculty members who are usually busy and time-constrained by clinical commitments. We aim to evaluate electronic feedback (e-feedback) after video observation of surgical suturing in comparison with standard face-to-face verbal feedback. METHODS: A prospective, blinded, randomized controlled trial comparing e-feedback with standard verbal feedback was carried out in February 2015 using a validated pro formas for assessment. The study participants were 38 undergraduate medical students from the University of Sheffield, UK. They were recorded on video performing the procedural skill, completed a self-evaluation form, and received e-feedback on the same day (group 1); observed directly by an assessor, invited to provide verbal self-reflection, and then received standard verbal feedback (group 2). In both groups, the feedback was provided after performing the procedure. The participants returned 2 days later and performed the same skill again. Poststudy questionnaire was used to assess the acceptability of each feedback among the participants. RESULTS: Overall, 19 students in group 1 and 18 students in group 2 completed the study. Although there was a significant improvement in the overall mean score on the second performance of the task for all participants (first performance mean 11.59, second performance mean 15.95; p ≤ 0.0001), there was no difference in the overall mean improvement score between group 1 and group 2 (4.74 and 3.94, respectively; p = 0.49). The mean overall scores for the e-feedback group at baseline recorded by 2 independent investigators showed good agreement (mean overall scores of 12.84 and 11.89; Cronbach α = 0.86). Poststudy questionnaire demonstrated that both e-feedback and standard verbal feedback achieved high mean Likert grades as recorded by the participants (4.42 [range: 2-5] and 4.71 [range: 4-5], respectively; p = 0.274). CONCLUSION: e-Feedback after watching a video recording appears to be acceptable and is not quantitatively different than standard feedback in improving suturing skills among novice trainees. Video assessment of procedural skills is reliable.

Assessing the Nontechnical Skills of Surgical Trainees: Views of the Theater Team.

OBJECTIVE: This study aims to explore the views of members of theater teams regarding the proposed introduction of a workplace-based assessment of nontechnical skills of surgeons (NOTSS) into the Intercollegiate Surgical Curriculum Programme in the United Kingdom. In addition, the previous training and familiarity of the members of the surgical theater team with the concept and assessment of NOTSS would be evaluated. DESIGN: A regional survey of members of theater teams (consultant surgeons, anesthetists, scrub nurses, and trainees) was performed at 1 teaching and 2 district general hospitals in South Yorkshire. RESULTS: There were 160 respondents corresponding to a response rate of 81%. The majority (77%) were not aware of the NOTSS assessment tool with only 9% of respondents reporting to have previously used the NOTSS tool and just 3% having received training in NOTSS assessment. Overall, 81% stated that assessing NOTSS was as important as assessing technical skills. Trainees attributed less importance to nontechnical skills than the other groups (p ≤ 0.016). Although opinion appears divided as to whether the presence of a consultant surgeon in theater could potentially make it difficult to assess a trainee's leadership skills and decision-making capabilities, overall 60% agree that the routine use of NOTSS assessment would enhance safety in the operating theater and 80% agree that the NOTSS tool should be introduced to assess the nontechnical skills of trainees in theater. However, a significantly lower proportion of trainees (45%) agreed on the latter compared with the other groups (p = 0.001). CONCLUSIONS: Our survey demonstrates acceptability among the theater team for the introduction of the NOTSS tool into the surgical curriculum. However, lack of familiarity highlights the importance of faculty training for assessors before such an introduction.

Developing assessments of surgical skills for the GMC Performance Procedures.

INTRODUCTION: The objectives were to: (i) establish how 'typical' consultant surgeons perform on 'generic' (non-specialist) surgical simulations before their use in the General Medical Council's Performance Procedures (PPs); (ii) measure any differences in performance between specialties; and (iii) compare the performance of group of surgeons in the PPs with the 'typical' group. VOLUNTEERS AND METHODS: Seventy-four consultant volunteers in gastrointestinal surgery (n=21), vascular surgery (n=11), urology (n=10), orthopaedics (n=15), cardiothoracic surgery (n=10) and plastic surgery (n=7), plus 9 surgeons undertaking phase 2 of the PPs undertook 7 simple simulations in the skills laboratory. The scores of the volunteers were analysed by simulation and specialty using ANOVA. The scores of the volunteers were then compared with the scores of the surgeons in the PPs. RESULTS: There were significant differences between simulations, but most volunteers achieved scores of 75-100%. There was a significant simulation by specialty interaction indicating that the scores of some specialties differed on some simulations. The scores of the group of surgeons in the PPs were significantly lower than the reference group for most simulations. CONCLUSIONS: Simple simulations can be used to assess the basic technical skills of consultant surgeons. The simulation by specialty interaction suggests that whilst some skills may be generic, others are not. The lower scores of the surgeons in the PPs suggest that these tests possess criterion validity, i.e. they may help to determine when poor performance is due to lack of technical competence.